In tomorrow's (July 1) issue of Genes & Development, Siu Sylvia Lee, of the department of molecular biology and genetics at Cornell University in Ithaca, NY, and Gary Ruvkun, of the department of genetics at Harvard Medical School, report ?the first genome-wide functional genomic screen for longevity genes.?

The two teams used a library of 16,475 RNA interference constructs (created by Julie Ahringer at the University of Cambridge, UK) to inactivate genes in the nematode, Caenorhabditis elegans. Their analysis yielded a list of 89 candidate genes, 33 of which have clear orthologs in fruit fly, mouse, or humans, suggesting evolutionary conservation of aging's regulators.

The findings, Ruvkun told me, mark the insulin-signaling pathway as a potent arbiter of longevity in the worm. So, for instance, ablation of the age-1 (phosphatidylinositol 3- and 4-kinase) and akt-1 (serine/threonine kinase) genes both resulted in ?robust lifespan extension? ? the age-1 knockout worms lived 31.5 days, compared to a control lifespan of about 18.5 days.

But, Ruvkin said, ?I think it?s the new genes that we don?t know how to think about that that are most exciting.? Some 20 or so genes identified in the screen have no known biological function.

Next up: Tagging the genes with green fluorescent protein to monitor their expression and localization during the aging process. ?The first step is to generate lists,? he said. ?The second step is to sort those lists into pathways, and that?s a lot more work.?